KEYTRUDA SOLUTION FOR INFUSION 25MG/ML

MSD PHARMA (SINGAPORE) PTE. LTD.

MSD PHARMA (SINGAPORE) PTE. LTD.

Therapeutic

Prescription Only

INFUSION, SOLUTION CONCENTRATE

**2\. DOSAGE AND ADMINISTRATION** **2.1 General** **Patient Selection** _For single-agent treatment of Non-Small Cell Lung Carcinoma, Urothelial Carcinoma, or Colorectal Cancer._ Select patients for treatment with KEYTRUDA based on the presence of positive PD-L1 expression _\[see Clinical Studies (9)_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_ in: - locally advanced or metastatic NSCLC. - locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. Select patients for treatment with KEYTRUDA based on microsatellite instability-high cancer (MSI-H) or mismatch repair deficient (dMMR) tumor status _\[see Clinical Studies (9)_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_ in: - metastatic CRC. _For treatment of TNBC in combination with chemotherapy_ Select patients for treatment with KEYTRUDA based on the presence of positive PD-L1 expression _\[see Clinical Studies (9)_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_ in: - locally recurrent unresectable or metastatic TNBC. _For treatment of cervical cancer in combination with chemotherapy, with or without bevacizumab_ Select patients for treatment with KEYTRUDA based on the presence of positive PD-L1 expression _\[see Clinical Studies (9)_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_ in: - persistent, recurrent, or metastatic cervical cancer. **Recommended Dosing** KEYTRUDA is administered as an intravenous infusion over 30 minutes. The recommended dose of KEYTRUDA in adults with HNSCC, cHL, urothelial carcinoma, esophageal carcinoma, CRC, HCC, cervical cancer, RCC, endometrial carcinoma, TNBC, previously untreated NSCLC, or for the adjuvant treatment of melanoma, NSCLC or RCC is either: - 200 mg every 3 weeks or - 400 mg every 6 weeks. The recommended dose of KEYTRUDA in adults with previously treated NSCLC or for unresectable or metastatic melanoma is 2 mg/kg every 3 weeks. For use in combination, see the prescribing information for the concomitant therapies. When administering KEYTRUDA as part of a combination with intravenous chemotherapy, KEYTRUDA should be administered first. For RCC patients treated with KEYTRUDA in combination with axitinib, see the prescribing information regarding dosing of axitinib. When used in combination with KEYTRUDA, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of six weeks or longer _\[see Clinical Studies (9)_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_ _\]_. For endometrial carcinoma and RCC patients treated with KEYTRUDA in combination with lenvatinib, the recommended initial dose of lenvatinib is 20 mg orally once daily until disease progression or unacceptable toxicity. Patients should be treated with KEYTRUDA until disease progression or unacceptable toxicity. Atypical responses (i.e., an initial transient increase in tumor size or small new lesions within the first few months followed by tumor shrinkage) have been observed. Clinically stable patients with initial evidence of disease progression should remain on treatment until disease progression is confirmed. For the adjuvant treatment of melanoma, NSCLC or RCC, KEYTRUDA should be administered for up to one year or until disease recurrence or unacceptable toxicity. For the neoadjuvant and adjuvant treatment of high-risk early-stage TNBC, patients should be treated with neoadjuvant KEYTRUDA in combination with chemotherapy for 8 doses of 200 mg every 3 weeks or 4 doses of 400 mg every 6 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as monotherapy for 9 doses of 200 mg every 3 weeks or 5 doses of 400 mg every 6 weeks or until disease recurrence or unacceptable toxicity. Patients who experience disease progression that precludes definitive surgery or unacceptable toxicity related to KEYTRUDA as neoadjuvant treatment in combination with chemotherapy should not receive KEYTRUDA monotherapy as adjuvant treatment. **Dose Modifications** No dose reductions of KEYTRUDA are recommended. Withhold or discontinue KEYTRUDA to manage adverse reactions as described in Table 1.  In patients with cHL with Grade 4 hematological toxicity, KEYTRUDA should be withheld until adverse reactions recover to Grades 0–1. In patients with RCC being treated with KEYTRUDA in combination with axitinib: - If ALT or AST ≥ 3 times ULN but <10 times ULN without concurrent total bilirubin ≥ 2 times ULN, withhold both KEYTRUDA and axitinib until these adverse reactions recover to Grades 0–1. Consider corticosteroid therapy. Consider rechallenge with a single drug or sequential rechallenge with both drugs after recovery. If rechallenging with axitinib, consider dose reduction as per the axitinib prescribing information. - If ALT or AST ≥ 10 times ULN or >3 times ULN with concurrent total bilirubin ≥ 2 times ULN, permanently discontinue both KEYTRUDA and axitinib and consider corticosteroid therapy. When administering KEYTRUDA in combination with lenvatinib, interrupt one or both or dose reduce or discontinue lenvatinib to manage adverse reactions as appropriate. For recommendations for management of adverse reactions of lenvatinib, refer to the prescribing information for lenvatinib. No dose reductions are recommended for KEYTRUDA. **Preparation and Administration** - Protect from light. Do not freeze. Do not shake. - Equilibrate the vial of KEYTRUDA to room temperature. - Prior to dilution, the vial of liquid can be out of refrigeration (temperatures at or below 25°C) for up to 24 hours. - Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. KEYTRUDA is a clear to slightly opalescent, colorless to slightly yellow solution. Discard the vial if visible particles are observed. - Withdraw the required volume up to 4 mL (100 mg) of KEYTRUDA and transfer into an intravenous bag containing 0.9% sodium chloride or 5% glucose (dextrose) to prepare a diluted solution with a final concentration ranging from 1 to 10 mg/mL. Mix diluted solution by gentle inversion. - Do not freeze the infusion solution. - The product does not contain preservative. The diluted product should be used immediately. If not used immediately, diluted solutions of KEYTRUDA may be stored at room temperature (at or below 25°C) for a cumulative time of up to 6 hours. Diluted solutions of KEYTRUDA may also be stored under refrigeration at 2°C to 8°C; however, the total time from dilution of KEYTRUDA to completion of infusion should not exceed 96 hours. If refrigerated, allow the vials and/or IV bags to come to room temperature prior to use. - Translucent to white proteinaceous particles may be seen in the diluted solution. Administer infusion solution intravenously over 30 minutes using a sterile, non-pyrogenic, low-protein binding 0.2 to 5 micrometres in-line or add-on filter. - Do not co-administer other drugs through the same infusion line. - Discard any unused portion left in the vial. **2.2 Pediatric Patients** In melanoma and cHL, the recommended dose of KEYTRUDA in pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks. **2.3 Geriatric Patients** No overall differences in safety or efficacy were reported between elderly patients (65 years and over) and younger patients (less than 65 years). No dose adjustment is necessary in this population. **2.4 Renal Impairment** No dose adjustment is needed for patients with mild or moderate renal impairment. KEYTRUDA has not been studied in patients with severe renal impairment. **2.5 Hepatic Impairment** No dose adjustment is needed for patients with mild or moderate hepatic impairment. KEYTRUDA has not been studied in patients with severe hepatic impairment.